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ID PMID Title PublicationDate abstract
29438164 The autoimmune ecology: an update. 2018 Jul PURPOSE OF REVIEW: The autoimmune ecology refers to the interactions between individuals and their environment leading to a breakdown in immune tolerance and, therefore, to the development of one or more autoimmune diseases in such an individual. Herein, an update is offered on four specific factors associated with autoimmune diseases, namely, vitamin D, smoking, alcohol and coffee consumption from the perspective of exposome and metabolomics. RECENT FINDINGS: Smoking is associated with an increased risk for most of the autoimmune diseases. Carbamylation of proteins as well as NETosis have emerged as possible new pathophysiological mechanisms for rheumatoid arthritis. Low-to-moderate alcohol consumption seems to decrease the risk of systemic lupus erythematosus and rheumatoid arthritis, and studies of vitamin have suggested a beneficial effect on these conditions. Coffee intake appears to be a risk factor for type 1 diabetes mellitus and rheumatoid arthritis and a protective factor for multiple sclerosis and primary biliary cholangitis. SUMMARY: Recent studies support the previously established positive associations between environmental factors and most of the autoimmune diseases. Nevertheless, further studies from the perspective of metabolomics, proteomics and genomics will help to clarify the effect of environment on autoimmune diseases.
29029308 Difficult-to-treat rheumatoid arthritis: an area of unmet clinical need. 2018 Jul 1 Increased effectiveness of pharmacological treatments in early RA has led many to believe that difficult-to-treat, established RA is a condition of the past. However, there are still plenty of RA patients who continue to have signs and symptoms suggestive of inflammatory disease activity, despite consecutive treatment with multiple conventional synthetic and biological DMARDs. We argue that difficult-to-treat RA constitutes an area of unmet clinical need and propose a definition of this concept. An overview of what is known about the multiple contributory factors varying for each individual patient, and an approach towards improved patient-tailored management are presented. This management approach involves thorough assessment to determine whether persistence of signs and symptoms is based on inflammatory disease activity, and the role of comorbidities. Furthermore, it addresses medication-related issues, such as non-adherence, patient beliefs and expectations, and setting of realistic treatment goals.
29507629 Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in 2018 Objectives: Mesenchymal stem cells (MSCs) release extracellular vesicles (EVs) that display a therapeutic effect in inflammatory disease models. Although MSCs can prevent arthritis, the role of MSCs-derived EVs has never been reported in rheumatoid arthritis. This prompted us to compare the function of exosomes (Exos) and microparticles (MPs) isolated from MSCs and investigate their immunomodulatory function in arthritis. Methods: MSCs-derived Exos and MPs were isolated by differential ultracentrifugation. Immunosuppressive effects of MPs or Exos were investigated on T and B lymphocytes in vitro and in the Delayed-Type Hypersensitivity (DTH) and Collagen-Induced Arthritis (CIA) models. Results: Exos and MPs from MSCs inhibited T lymphocyte proliferation in a dose-dependent manner and decreased the percentage of CD4(+) and CD8(+) T cell subsets. Interestingly, Exos increased Treg cell populations while parental MSCs did not. Conversely, plasmablast differentiation was reduced to a similar extent by MSCs, Exos or MPs. IFN-γ priming of MSCs before vesicles isolation did not influence the immunomodulatory function of isolated Exos or MPs. In DTH, we observed a dose-dependent anti-inflammatory effect of MPs and Exos, while in the CIA model, Exos efficiently decreased clinical signs of inflammation. The beneficial effect of Exos was associated with fewer plasmablasts and more Breg-like cells in lymph nodes. Conclusions: Both MSCs-derived MPs and Exos exerted an anti-inflammatory role on T and B lymphocytes independently of MSCs priming. However, Exos were more efficient in suppressing inflammation in vivo. Our work is the first demonstration of the therapeutic potential of MSCs-derived EVs in inflammatory arthritis.
29340266 (18)F-FDG PET-CT in a patient with methotrexate-associated lymphoproliferative disorder. 2018 Jan (18)F-FDG PET-CT clearly demonstrated the disease activity of MTX-LPD.
30273649 A case of Histoplasma capsulatum variety capsulatum septic arthritis successfully treated 2018 Dec Histoplasma capsulatum variety capsulatum (H. capsulatum) is a thermally dimorphic fungus that is endemic to the Mississippi River and Ohio River valley regions. Of the hundreds of thousands of patients exposed to this fungus, less than 1% develop a severe illness most commonly manifesting as pulmonary disease. Septic arthritis from hematogenous seeding with H. capsulatum or from direct inoculation has been reported only rarely in the literature. The first case of septic arthritis of the shoulder due to H. capsulatum occurring in an immunocompromised patient, treated successfully with irrigation and debridement, systemic antifungals, and local delivery of amphotericin B with cement beads, is reported here. Importantly, the addition of local amphotericin B delivery by cement beads to conventional treatment likely led to clinical cure in this patient.
29876652 The emerging role of cardiovascular magnetic resonance imaging in the assessment of cardia 2018 Aug Juvenile idiopathic arthritis (JIA) is the commonest rheumatic disease in childhood and presents several subtypes according to the ILAR classification. JIA, specifically in its systemic form, may seriously damage various structures of the cardiovascular system. Other JIA phenotypes are also of interest, as cardiovascular disease (CVD) is underestimated and understudied, but chronic systemic inflammation and risk factors remained important contributors for CVD development. The currently applied non-invasive modalities, although they are important for the initial evaluation of JIA patients, frequently fail to detect the silent, subclinical forms of CVD. Cardiovascular magnetic resonance (CMR), due to its multifaceted capability in the detection of cardiovascular disease, can offer early, reproducible, non-invasive information about cardiovascular disease in JIA, allowing risk stratification and timely initiation /modification of cardiologic and anti-rheumatic treatment. However, lack of availability/expertise and high cost still hamper its application in the clinical cardio-rheumatic practice. The aim of the current article is to present an overview of CVD in JIA emphasizing the emerging role of CMR in early diagnosis and treatment follow-up of CVD in JIA patients.
29904314 Cutaneous toxicity of oral low-dose methotrexate. 2018 Jul Chemotherapy-induced acral erythema has been a known side effect of intravenous dosing but has not been reported with oral therapy. Herein we describe two patients receiving treatment with low-dose oral methotrexate who presented with acral erythema. Clinicians and rheumatologists should be aware of this potentially serious side effect of oral chemotherapy in various patient populations. This complication related to methotrexate, though rare, should be anticipated in patients on multiple medications who develop mucocutaneous toxicities.
29862045 Comparison between low disease activity or DAS remission as treatment target in patients w 2018 OBJECTIVES: To compare outcomes of targeted treatment aimed at either low disease activity or remission in patients with early active rheumatoid arthritis (RA). METHODS: Five-year outcomes were compared in 133 patients with early active RA (1987), starting with methotrexate, sulfasalazine and tapered high dose of prednisone (arm 3 of the BehandelStrategieën (Treatment Strategies for Rheumatoid Arthritis) (BeSt) study), targeted at Disease Activity Score (DAS) ≤2.4 (low disease activity), and 175 patients with early RA, starting methotrexate and tapered high dose of prednisone, targeted at DAS <1.6 (selected from IMPROVED study who would have fulfilled inclusion criteria of the BeSt study). Association of treatment target with outcomes DAS <1.6, Boolean remission at year 1 and drug-free DAS remission (DFR) at year 5 were analysed by logistic regression analysis. RESULTS: At baseline, DAS <1.6 steered patients had a milder disease than DAS ≤2.4 steered patients (mean DAS 4.1±SD 0.7vs4.4±0.9, p=0.012) and less radiological damage. DAS decrease, functional ability and radiological damage progression over time were similar in both patient groups. DAS ≤2.4 was achieved in similar percentages in both patient groups, but more DAS <1.6 steered patients achieved DAS <1.6 and DFR. DAS <1.6 steered treatment was associated with achieving DAS <1.6 (OR 3.04 (95% CI 1.64 to 5.62)) and Boolean remission (3.03 (1.45 to 6.33)) at year 1 and DFR at year 5 (3.77 (1.51 to 9.43)). CONCLUSIONS: In patients with early active RA who start with comparable disease-modifying antirheumatic drug+prednisone combination therapy, subsequent DAS <1.6 steered treatment is associated with similar clinical and radiological outcomes over time as DAS ≤2.4 steered treatment; however, in the DAS <1.6 steered group, more patients achieved remission and drug-free remission.
30568700 Effect of Losartan in Complete Freund's Adjuvant -Induced Arthritis in Rats. 2018 Fall Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by joint infiltration and bone damage. The aim of the present study was to evaluate the beneficial effects of losartan in adjuvant-induced arthritis (AIA). Arthritis was induced in rats by subcutaneous injection of 0.2 mL of Complete Freund's adjuvant (CFA) in the planter surface of the hind paw. Arthritic rats were allocated into three groups (n = 10), the first group (arthritis control), received 1% of tween 80, the second and the third groups received prednisolone (10 mg/kg/day; p.o) and losartan (20 mg/kg/day; p.o) respectively for two weeks. A fourth group (vehicle control) received 1% tween 80. At the end of the experiment, blood samples were collected for biochemical, oxidative stress, and hematological analysis. Histopathological and macroscopical examinations on joints were also performed. Our results revealed that losartan significantly reduced serum levels of tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6) , rheumatoid factor (RF), and erythrocytes sedimentation rate (ESR).It significantly decreased serum malondialdehyde and increased blood glutathione .Losartan exhibited significant decrease in serum level of total cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL) coupled with marked increase in high density lipoprotein (HDL).Furthermore, losartan decreased white blood cell cells (WBC's) count and increased red blood cells (RBC's) , hemoglobin (Hb) , platelets, and hematocrit (Hct) counts. These findings were further supported by histopathological and macroscopical examinations. It could be concluded that losartan was able to repress biochemical, oxidative and hematological changes associated with AIA. These effects could be attributed to anti-arthritic, hypolipidemic, antioxidant and anti-anemic properties.
31364981 Comprehensive review of current diagnostic and treatment approaches to interstitial lung d 2019 Jul Interstitial lung disease (ILD) is one of the extra-articular involvement forms of rheumatoid arthritis (RA), and it is associated with increased mortality. The presence of genetic susceptibility, smoking, rheumatoid factor positivity, and the presence of anticitrulline peptide antibodies are factors contributing to the development of ILD in patients with RA. Early diagnosis and treatment of ILD contribute to the reduction of morbidity and mortality. We herein evaluated the current literature for the diagnosis and treatment of RA-associated ILD.
30017344 Autoimmune associations in a Mexican cohort with primary biliary cholangitis. 2019 Apr INTRODUCTION: Several groups have reported associations of primary biliary cholangitis with other autoimmune entities, particularly Sjögren's syndrome and hypothyroidism. Its prevalence and characteristics in Mexican patients is unknown. AIM: To determine the frequency and characteristics of autoimmune diseases in a Mexican cohort of patients with primary biliary cholangitis. MATERIALS AND METHODS: The medical records of patients that presented with primary biliary cholangitis within the time frame of 2005 and 2012 were reviewed and assessed for other autoimmune diseases. RESULTS: Seventy-eight patients, 75 women and 3 men, were included. Their mean age was 55.8 years. Seventy-three cases had positive antimitochondrial antibodies (94.8%) and disease was confirmed in 5 through liver biopsy. Five patients (8%) had anti-smooth muscle antibodies and 55/78 (70.5%) had antinuclear antibodies by indirect immunofluorescence. Forty-nine patients (62.8%) were positive for an autoimmune disease other than primary biliary cholangitis. Among those, 20 patients had one associated disease, 14 had 2, and 15 patients had 3 concomitant diseases. They included: Sjögren's syndrome in 23/78 patients (29.5%), dysthyroidism in 21/78 cases (26.9%), Raynaud syndrome in 11/78 (14.1%), CREST syndrome in 9/78 patients (11.4%), rheumatoid arthritis in 6/78 patients (7.7%), vitiligo in 5/78 (6.4%), scleroderma in 4/78 patients (5.1%), and other diseases in 8 patients. In 12/78 patients (15.4%), there was a documented family background of autoimmune disease. CONCLUSIONS: The presence of autoimmune associations in our cohort was frequent, and similar in characteristics to the information reported by other groups. The clinical implications of those findings remain to be determined.
29782593 (18)F- FDG PET/CT joint assessment of early therapeutic response in rheumatoid arthritis p 2018 BACKGROUND: (18)F-FDG PET/CT has been proposed in the evaluation of the disease activity in rheumatoid arthritis (RA). The goals of this study were to evaluate the reproducibility of the technique, to compare metabolic parameters to clinical, biological and ultrasonographic parameters before and after treatment and to evaluate whether the early metabolic response was related to the outcome. (18)F- FDG PET/CT of the hands, wrists and knees was obtained in 15 patients with anti-TNFα refractory RA, at baseline and 16 weeks after treatment with rituximab. The number of PET-positive joints (PET+ joints), the cumulative standard uptake value (cSUV) and the composite index (CI) were defined. The composite clinical index DAS(28), CRP serum levels and the number of joints positive at ultrasonography (US+ joints) and the cumulative synovial thickness (CST) were also assessed at baseline and week 24. RESULTS: High interobserver agreement was observed, both at baseline and after treatment. The number of PET+ joints was not correlated with the number of joints tender or swollen. The 3 metabolic parameters were strongly correlated with US, CRP and DAS(28) at baseline and with US and CRP (CSUV, CI) at week 16, but no longer with the DAS(28) index. The metabolic response based on the change in the visual PET/CT joint analysis predicted the outcome with a high negative predictive value of 91%, with a 91% specificity, and an 86% accuracy. CONCLUSIONS: These preliminary data suggest that (18)F- FDG PET/CT is a reproducible and accurate tool for evaluating disease activity in refractory rheumatoid arthritis and its non-response to rituximab. The correlation obtained with US joint assessment gives relevance to objective diseased joints through imaging techniques.
29765284 Influence of serum leptin levels and Q223R leptin receptor polymorphism on clinical charac 2018 Apr OBJECTIVE: The aim of the present study was to evaluate the possible association between the Q223R Leptin receptor (LEPR) polymorphism (A>G; rs1137101) and leptin levels in patients with rheumatoid arthritis (RA) from Western Mexico. METHODS: A cross-sectional study was performed with 70 RA patients and 74 controls subject (CS). Disease activity was evaluated using DAS28 score, the Q223R LEPR polymorphism was determined by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and serum leptin levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) were quantified. RESULTS: RA patients had significant high serum leptin levels compared with CS; leptin levels correlated strongly with body composition measures, but not with inflammatory markers, disease evolution, and activity. The genotype and allele frequencies of the Q223R LEPR polymorphism were not associated with RA. Similarly, leptin levels did not differ between Q223R LEPR genotypes. CONCLUSION: The LEPR Q223R polymorphism was not associated with RA risk in patients from Mexican population, even though high levels of serum leptin were present and these could explain the low weight observed in RA patients when they were compared to control subjects. However, the serum leptin levels did not correlate with inflammatory markers, severity and disease evolution.
30911249 Effects of Conventional and Biological Drugs Used for the Treatment of Rheumatoid Arthriti 2019 Feb OBJECTIVE: This study aims to investigate the effects of conventional and biological drugs used for the treatment of rheumatoid arthritis (RA) on patients' quality of life, depression, and anxiety. MATERIALS AND METHODS: A total of 80 patients with a diagnosis of RA based on the American College of Rheumatology/Annual European Congress of Rheumatology (ACR/EULAR) 2010 diagnostic criteria were included in the study. Patients were classified into two groups as follows: patients using conventional disease-modifying agents (csDMARDs) alone (Group 1, n=40) and patients using biological disease-modifying agents (bDMARDs) and a csDMARD combination (Group 2, n=40). Demographical patient data were collected. The levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were measured in both groups. All patients completed the Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ), Short Form-36 (SF-36), Beck Depression Scale (BDS), and Hospital Anxiety Depression Scale (HADS). RESULTS: There was no significant difference between the two groups of patients regarding their demographical characteristics, autoantibody positivity, or DAS scores (p>0.05). HAQ scores and all parameters and summary scores of the SF-36, BDS, and HADS scores were not significantly different between the two groups (p>0.05). CONCLUSION: Results of the present study showed that csDMARDs and bDMARDs, which required a more invasive administration and were associated with serious side effects, were not superior to each other in terms of their effects on patients' quality of life. csDMARD and bDMARD were also not superior to each other regarding their effects on anxiety and depression among patients with RA.
29753098 Anti-arthritic activities of ethanol extracts of Circaea mollis Sieb. & Zucc. (whole plant 2018 Oct 28 ETHNOPHARMACOLOGICAL RELEVANCE: Circaea mollis Sieb. & Zucc., a genus of Circaea that follows Onagraceae, has been used for centuries as a folk herb in traditional Chinese medicine (TCM) and Hani Ethnopharmacy for the treatment of joint swelling and pain in rheumatoid arthritis. AIM OF THE STUDY: This study was designed to confirm anti-arthritic effects and its underlying mechanism of ethanol extracts of Circaea mollis Sieb. & Zucc. (EEC), which may contribute to provide the pharmacological basis in the treatment of rheumatoid disease. MATERIALS AND METHODS: Dimethylbenzene (DMB)-induced inflammatory swelling model, hot-plate pain model in mice and Freund's complete adjuvant (FCA)-induced arthritis model in rats were used to evaluate the anti-arthritis effect of EEC. Arthritis severity was done by measuring inflammatory swelling, pain threshol, paw swelling, arthritis index, body weight, spleen index and thymus index. The levels of TNF-α, IL-1β and IL-10 in sera were measured using ELISA. The pathological change of the ankle joint was also done. Phenolic composition of EEC was analyzed. RESULTS: EEC inhibited inflammatory swelling and increased heat-induced pain threshold in mice. Furthermore, EEC significantly alleviated paw swelling and arthritis index, decreasing the spleen index and thymus index. Besides, EEC down-regulated the serum TNF-α and IL-1β, and increased the production of serum IL-10 in FCA-induced rats. Histopathological examination demonstrated that EEC can effectively relieve synovial hyperplasia, control the infiltration of the inflammatory and protect cartilage from destruction. CONCLUSION: Our work demonstrated that EEC possessed the potential therapeutic effect against arthritis in rodents which was attributed to modulating proinflammatory cytokines TNF-α, IL-1β and anti-inflammatory factors IL-10. Flavonoids and polyphenols may contribute to the therapeutic effect of EEC on arthritis.
30496633 Resveratrol inhibits Src tyrosine kinase, STAT3, and Wnt signaling pathway in collagen ind 2019 Jan Resveratrol, a phytochemical, acts several cellular signaling pathways and has anti-inflammatory potentials. The purpose of this study is to research the therapeutic effect of resveratrol in collagen-induced arthritis (CIA) model in rats and whether resveratrol affects the activities of signaling pathways those are potent pathogenic actors of rheumatoid arthritis. Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant in Wistar albino rats. One day after the onset of arthritis (day 14), resveratrol (20 mg/kg/day) was given via oral gavage, until day 29. The paws of the rats were obtained for further analysis. Tissue Wnt5a, mitogen-activated protein kinase (MAPK), Src tyrosine kinase and signal transducer, and activator of transcription-3 (STAT3) mRNA expressions were determined by real-time polymerase chain reaction. Resveratrol ameliorated the clinical and histopathological (perisynovial inflammation and cartilage-bone destruction) findings of inflammatory arthritis. The tissue mRNA expressions of Wnt5a, MAPK3, Src kinase, and STAT3 were increased in the sham group compared to the control group. Resveratrol supplement decreased their expressions. The present study shows that Src kinase, STAT3, and Wnt signaling pathway are active in the CIA model. Resveratrol inhibits these signaling pathways and ameliorates inflammatory arthritis. © 2018 BioFactors, 45(1):69-74, 2019.
29371777 Pre-micro RNA-499 Gene Polymorphism rs3746444 T/C is Associated with Susceptibility to Rhe 2018 Jan Pre-miRNA-499 gene is associated with autoimmune disease. Mir-449 rs3746444 polymorphism is inconsistent for rheumatoid arthritis (RA). This study aimed to investigate association of mir-499 rs3746444 polymorphism with RA activity and severity in Egyptian population. The study population was conducted as case control study in 100 RA patients diagnosed according to the American College of Rheumatology classification criteria for RA, and the control group included 100 healthy subjects who were age-and sex-matched to the RA group. Different genotypes were assessed using polymerase chain reaction-restriction fragment length polymorphism. 95% Confidence interval and odds ratio were defined to assess the strength of association. Regarding patients, thirty-three patients carried TT genotype, fifty-three patients carried TC genotype and fourteen patients carried CC genotype. So the frequency of the minor C allele in RA patients was significantly higher than the control subjects (P = 0.037). TC, CC genotypes and C allele frequencies were significantly associated with disease severity as they had high rheumatoid factor (55.78 µIU/ml) and anti-cyclic citrullinated peptide (Anti-CCP) antibody (297.32 µIU/ml). Moreover, the heterozygote TC had more severe and more active form of the disease compared with homozygote CC or TT as they had high Anti-CCP antibody, and disease activity score 28 (score 5). Our work suggests that C allele of Pre-miRNA rs3746444 polymorphism contributes to heritability of susceptibility to RA compared to T allele. This polymorphism was associated with the activity and severity of the disease.
30701944 Cardiovascular safety of non-steroidal anti-inflammatory drugs in chronic inflammatory rhe 2018 Aug 27 Rheumatic diseases (RD), such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, vasculitis, gout are associated with increase in cardiovascular morbidity and mortality. The main causes of increased cardiovascular risk are inflammatory heart and vascular lesions, accelerated progression of atherosclerosis and side effects of drug therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in clinical practice and are on the list of the most prescribed medications. It is known that NSAIDs have a negative effect on the cardiovascular system (CVS). However NSAIDs may decrease the intensity of inflammation, which is an independent risk risk factor for CVS pathology. Therefore in patients with RD it is theoretically possible to reduce the severity of cardiovascular side effects when using NSAIDs. The article discusses the issues of NSAID's cardiovascular safety, the molecular mechanisms underlying the negative effect of them on CVS, critically evaluated the results of main studies concerning the cardiovascular safety of NSAIDs in chronic inflammatory diseases.
29074297 Hierarchical, imbalanced pro-inflammatory cytokine networks govern the pathogenesis of chr 2018 Jan BACKGROUND: Chronic inflammatory arthropathies, such as rheumatoid arthritis (RA), spondyloarthritis, including psoriatic arthritis (PsA), ankylosing spondyloarthritis (AS), osteoarthritis (OA), and intervertebral disc degenerative disease (DDD) constitute major public health problems that are anticipated to grow significantly as the human population ages. However, many aspects concerning the molecular mechanisms underlying their onset and progression remain unclear. DESIGN: This narrative review critically analyzes the molecular mechanisms underlying the inflammation-associated pathogenesis of the aforementioned joint diseases. This includes, in particular, the major role played by several key soluble factors (such as cytokines and the associated signaling pathways, designated as "fragile nodes") produced by local cells and recruited to the joints' immune cells, whose elimination by specific drugs has dramatically improved the diseases' symptomatology and outcome in human clinical trials or in rodent arthritis models. HYPOTHESIS AND THE AIM OF THIS REVIEW: We hypothesize that the pathogenesis of chronic inflammatory arthropathies is governed by hierarchical, imbalanced pro-inflammatory cytokine networks (HIPICNs) (comprising a combination of fragile nodes) that are created during the development of both autoimmune (RA, PsA, and AS) and non-autoimmune (OA and DDD) disorders. The main aim of this review is to provide evidence that despite substantial pathobiological differences between these arthropathies, the HIPICNs created are quite common, thus justifying the merging of these disorders mechanistically and suggesting that these common mechanisms exist in the onset and progression of different joint diseases.
30327685 New insights and long-term safety of tocilizumab in rheumatoid arthritis. 2018 Oct Rheumatoid arthritis is a leading musculoskeletal cause of disability in Western society. Therapeutic options have expanded rapidly with the advent of biological agents as treatment options. One of these, tocilizumab, targets the interleukin-6 receptor and has been approved since the late 2000s in many jurisdictions. This approval was based on 6-12 month trials. It is now appropriate to look at longer-term studies and what new insights they have provided into this agent. Data are based largely on observational studies with their well-known limitations as well as some further randomized trials and provide a number of important observations regarding both efficacy and safety. In conclusion, the longer-term data suggest tocilizumab efficacy increases over time for both signs and symptoms and radiographic change. It is also corticosteroid sparing. The safety data are consistent with the shorter-term trials and are largely reassuring but some questions still remain over cardiovascular safety and cancer risk.